Abstract
Natural killer cells (NK) secrete eosinophilotactic cytokines, however, whether they contribute to eosinophil chemotaxis by secreting IL-8 is not known. We investigated the ability of CD56+CD3-ve (NK cells) to induce chemotaxis of peripheral blood eosinophils from allergic rhinitis (AR) patients, through IL-8 secretion, and the effects of IL-15, the NK cell proactivating cytokine, and calcitriol: 1α, 25-dihydroxy Vitamin D3 (vitamin D3), the immunomodulator agent, in this scenario. Herein, it is shown that supernatants from unstimulated NK cells exhibited chemotactic activity against eosinophil. This effect was significantly augmented by IL-15 (1 ng/mL) treatment, resulting in an increase in the chemotactic index of approximately 3 folds and was abrogated by neutralizing antibody (Ab) to IL-8 in a dose-dependent fashion. The amount of IL-8 secreted by NK cells was increased by IL-15 treatment from levels of 88.64 ± 21.5 to 178.9 ± 23.6 Pg/mL and was significantly reduced by 10−6 M vitamin D3 to levels of 59.2 ± 16.3 Pg/mL. Our results indicate a novel inflammatory crosstalk between NK cells and eosinophils via IL-15/IL-8 axis that can be modulated by vitamin D3.
Highlights
IntroductionIL-8 possesses a clear role in eosinophil chemotaxis in allergic respiratory diseases [2, 3]
IL-8 is a potent activator for eosinophil chemotaxis in vitro and in vivo [1]
Natural killer cells (NK) cells were isolated from buffy coats to obtain large amount of cells for culture purposes, and eosinophils were freshly isolated from the peripheral blood of sixteen allergic rhinitis (AR) patients sensitized to different aeroallergens that were confirmed by skin tests and/or radioallergosorbent test (RAST)
Summary
IL-8 possesses a clear role in eosinophil chemotaxis in allergic respiratory diseases [2, 3]. The secretagogue activity of NK cells includes IFN-γ, IL10, TNF-α, MIP-1, MIP-1β, and GM-CSF. These cytokines are augmented by IL-15, a cytokine produced by activated monocytes/macrophages [12, 13]. A more recent study demonstrated the existence of type 2 cytokine-secreting NK cells in AR and showed increased number and enhanced cytotoxicity of NK cells [16]. This highlights a novel role for NK cells in allergic diseases. Whether NK cells are able to attract eosinophils through IL-8 secretion is not known
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